This research proposal targets the development of the first portable intra-operative digital specimen tomosynthesis system for rapid and accurate three-dimensional radiographic margin assessment of surgically excised breast tissue specimens during breast-conserving surgery (BCS). A three-dimensional radiographic margin assessment system, which can reliably predict macroscopic excision margin status while the patient is still in the operating room, could reduce both surgical re-excision and local recurrence rates associated with BCS. The proposed ex-vivo tomosynthesis system could also serve as a realistic test bed for assessing the clinical efficacy of tomosynthesis in three dimensional imaging of breast tissue, in anticipation of full-breast screening tomosynthesis systems currently under development. Specific Aim 1: Specify, design and integrate hardware components of an intra- operative tomosynthesis system optimized for surgically excised breast tissue specimens in BCS. Specific Aim 2: Specify, design and implement reconstruction algorithms optimized for rapid and accurate intra-operative tomosynthesis of surgically excised breast tissue specimens. Specific Aim 3: Integrate selected hardware and software components optimized for intra-operative tomosynthesis of surgically excised breast tissue specimens. Specific Aim 4: Quantify the integrated system's efficacy in a pre-clinical setting, utilizing simulated excised breast tissue samples and standard breast x-ray imaging phantoms. In Phase I of this research, we will utilize both computer-simulated and physical phantoms to quantify the efficacy of the device and associated software algorithms. In phase II, we will conduct a formal clinical trial to quantify any potential reduction in surgical re-excision rates attributable to the use of the intra-operative specimen tomosynthesis system developed and optimized in Phase I. PUBLIC HEALTH RELEVANCE: Studies have shown no significant difference in survival rates between women with breast cancer who are treated with radical mastectomy versus those treated with lumpectomy in conjunction with radiation therapy. However, surgical re-excision rates and local breast cancer recurrence rates in patients treated with lumpectomy and radiation therapy are at least twice as high as those treated with mastectomy. We propose to design and build a three-dimensional radiographic excision margin assessment system which can help reduce both surgical re-excision and local recurrence rates in breast cancer patients who select lumpectomy over mastectomy.